Abstract
Statins have both cholesterol lowering and antiinflammatory
activities, whether mechanisms underlying
their activities are independent remains unclear. The ATPgated
P2X4 receptor is a pro-inflammatory mediator. Here,
we investigate the action of fluvastatin and other cholesterol
depleting agents on native and recombinant human P2X4
receptor. Fluvastatin and mßCD suppressed P2X4-dependent
calcium influx in THP-1 monocytes, without affecting
P2Y receptor responses. mßCD or filipin III suppressed the
current density of recombinant human P2X4 receptors.
Human P2X2 was insensitive to cholesterol depletion. Cholesterol
depletion had no effect on intrinsic P2X4 receptor
properties as judged by ATP concentration–response relationship,
receptor rundown or current decay during agonist
occupancy. These data suggest fluvastatin suppresses P2X4
activity in monocytes through cholesterol depletion and not
by modulating intrinsic channel properties.
Original language | English |
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Pages (from-to) | 311-316 |
Number of pages | 6 |
Journal | Purinergic Signalling |
Volume | 8 |
Issue number | 2 |
DOIs | |
Publication status | Published - Jun 2012 |